Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States.

BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.

Photoprotection-related properties of a raw extract from Gordonia hongkongensis EUFUS-Z928: A culturable rare actinomycete associated with the Caribbean octocoral Eunicea fusca.

UV filters in current sunscreen formulations can have negative effects on human health, such as endocrine disruption and allergic reactions, as well as on the environment, including bioaccumulation and coral health toxicity. As a result, there is a need to find alternative compounds that serve as safer and more ecofriendly active ingredients. This study successfully isolated actinomycetes from the octocoral Eunicea fusca and assessed their potential as producers of photoprotective compounds. The use of bio-based chemical agents, particularly natural products, has been a highly effective strategy for discovering bioactive compounds, especially in marine invertebrates and their associated microbiota. Eighteen bacterial isolates were obtained and subsequently employed to prepare raw methanolic extracts from seven-day submerged cultures in Zobell marine broth. The resulting extracts were screened for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging capacity and characterized by total phenolic and flavonoid content measurements. After screening, the Gordonia hongkongensis EUFUS-Z928-derived raw extract exhibited the best antioxidant profile, i.e. DPPH and ABTS radical scavenging of 4.93 and 6.00 µmol Trolox per gram of extract, respectively, and selected for further photoprotection-related analysis. Thus, this extract demonstrated a UV-absorbing capacity of 46.33% of the in vitro sun protection factor calculated for 30 µg/mL oxybenzone but did not exhibit any cytotoxicity on human dermal fibroblasts (HDFa cell line) at concentrations up to 500 µg/mL. The liquid chromatography-mass spectrometry chemical characterization of this extract showed compounds with structural features associated with free radical scavenging and UV absorption (i.e. photoprotection-related activities). These findings highlighted the potential of the microbiota associated with E. fusca and confirmed the feasibility of exploiting its metabolites for photoprotection-related purposes.

Molecular and Clinicopathologic Impact of GNAS Variants Across Solid Tumors.

PURPOSE: The molecular drivers underlying mucinous tumor pathogenicity are poorly understood. GNAS mutations predict metastatic burden and treatment resistance in mucinous appendiceal adenocarcinoma. We investigated the pan-cancer clinicopathologic relevance of GNAS variants. METHODS: We assessed 58,043 patients with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT)-sequenced solid tumors to identify oncogenic variants, including GNAS, associated with mucinous tumor phenotype. We then performed comprehensive molecular analyses to compare GNAS-mutant (mut) and wild-type tumors across cancers. Gene expression patterns associated with GNAS-mut tumors were assessed in a The Cancer Genome Atlas cohort. Associations between GNAS variant status and peritoneal metastasis, first-line systemic therapy response, progression-free survival (PFS), and overall survival (OS) were determined using a propensity-matched subcohort of patients with metastatic disease. RESULTS: Mucinous tumors were enriched for oncogenic GNAS variants. GNAS was mutated in >1% of small bowel, cervical, colorectal, pancreatic, esophagogastric, hepatobiliary, and GI neuroendocrine cancers. Across these cancers, GNAS-mut tumors exhibited a generally conserved C-to-T mutation-high, aneuploidy-low molecular profile with co-occurring prevalent KRAS variants (65% of GNAS-mut tumors) and fewer TP53 alterations. GNAS-mut tumors exhibited recurrently comutated alternative tumor suppressors (RBM10, INPPL1) and upregulation of MAPK and cell surface modulators. GNAS-mut tumors demonstrate an increased prevalence of peritoneal metastases (odds ratio [OR], 1.7 [95% CI, 1.1 to 2.5]; P = .006), worse response to first-line systemic therapy (OR, 2.2 [95% CI, 1.3 to 3.8]; P = .003), and shorter PFS (median, 5.6 v 7.0 months; P = .047). In a multivariable analysis, GNAS mutated status was independently prognostic of worse OS (hazard ratio, 1.25 [95% CI, 1.01 to 1.56]; adjusted P = .04). CONCLUSION: Across the assessed cancers, GNAS-mut tumors exhibit a conserved molecular and clinical phenotype defined by mucinous tumor status, increased peritoneal metastasis, poor response to first-line systemic therapy, and worse survival.

Redefining feasibility in clinical trials: Collaborative approaches for improved site selection.

Background: This Site Feasibility Task Force convened to assess the complex and burdensome process of site feasibility in clinical trials. The objective was to create mutual understanding of challenges and provide suggestions for improving collaboration among sponsors, contract research organizations (CROs), and sites. Methods: The task force was composed of representatives from sponsors, CROs and sites (43 % Sites, 20 % Site Networks, 10 % Small/mid-size sponsors, 10 % Small/mid-size CROs, 10 % Large sponsors, 7 % Large CROs). The group collaborated to define the scope of the problem, identify challenges in the current process, and provide suggestions for improving the process. Results: The group found there is a need for better differentiation between the three main stages of feasibility, and the four sub-phases of Site Feasibility. The discussion brought to light emerging trends like early initiation of Site Feasibility and premature engagement of sites by CROs. To fully explain these challenges, the group analyzed the current practices and documented their downstream impact on clinical trial execution for all stakeholders. A list of best practices emerged naturally from this analysis. These findings are aggregated into short and actionable best practice guides. Conclusion: The task force suggests practical changes for the feasibility process and raises awareness of emerging trends and their associated risks. This awareness can begin to drive change in the site feasibility process, although industry-wide transformation will require new levels of collaboration, data standardization and automation tools. The potential benefits of evolving this process are significant and meaningful for more efficient and successful clinical trials.

Leptospirosis: A dual threat - predisposing risk for renal transplant and trigger for renal transplant dysfunction.

Leptospirosis (LTPS) is a bacterial infection that affects humans, often with mild or no symptoms. It is estimated that approximately 10 % of patients with LTPS may experience multi-organ dysfunction, including renal abnormalities. In regions where LTPS is widespread, a considerable number of instances involving acute kidney injury (AKI) and chronic kidney disease (CKD) of unknown etiology (CKDu) have been reported. Additionally, studies have shown a correlation between kidney graft dysfunction in patients with stable kidney transplants after LTPS. These findings indicate that exposure to LTPS may increase the likelihood of kidney transplantation due to the onset of both acute and chronic kidney injuries. Simultaneously, it poses a potential risk to the stability of kidney grafts. Unfortunately, there is limited scientific literature addressing this issue, making it difficult to determine the negative impact that LTPS may have, such as its role as a risk factor for the need of kidney transplantation or as a threat to individuals who have undergone kidney transplants. This study aims to shed light on the immune mechanisms triggered during LTPS infection and their importance in both kidney damage and allograft dysfunction.

Review article: Oesophageal disorders in chronic liver disease.

BACKGROUND: Oesophageal disorders and chronic liver disease are common worldwide and significantly impact quality of life. The intricate link between these conditions, including how oesophageal disorders like GERD, Barrett's oesophagus and oesophageal cancer affect and are affected by chronic liver disease, remains poorly understood. AIMS: To review the relationship between oesophageal disorders and chronic liver disease, evaluating epidemiology, pathophysiology and therapeutic factors. METHODS: We reviewed the literature on the relationship between oesophageal disorders and chronic liver disease, including cirrhosis, using the PubMed database RESULTS: Oesophageal disorders such as gastroesophageal reflux disease, Barrett's oesophagus, oesophageal cancer, oesophageal motor disorders and oesophageal candidiasis are prevalent among individuals with cirrhosis, exacerbating the burden of liver disease. These diseases have a multifaceted symptomatology and pathogenic basis, posing a significant challenge in cirrhotic patients that necessitates careful diagnosis and management. Additionally, therapies frequently used for these diseases, such as proton pump inhibitors, require careful consideration in cirrhotic patients due to potential adverse effects and altered pharmacokinetics. Managing oesophageal disorders in cirrhotic patients requires a cautious approach due to possible interactions with medications and the risk of adverse effects. Furthermore, symptoms associated with these conditions are often exacerbated by common interventions in patients with cirrhosis, such as band ligation for oesophageal varices. CONCLUSIONS: Oesophageal disorders are common in cirrhosis and increase the disease burden. These conditions require careful management due to complex symptoms and treatment risks. Proton pump inhibitors and other therapies must be used cautiously, as cirrhosis interventions can worsen symptoms.

Lipoprotein(a)'s Role in Atherosclerosis and Aortic Stenosis: A Contemporary Literature Review.

Lipoprotein(a), or Lp(a), is a distinctive lipoprotein particle linked to various cardiovascular diseases, notably atherosclerosis and aortic stenosis. Much like plasminogen, Lp(a) hinders normal fibrinolysis, leading to increased thrombosis and slower clearance of fibrin debris. It also causes inflammation, oxidative stress, and endothelial dysfunction, contributing to the formation of atherosclerotic lesions. Epidemiological studies have consistently shown that even slight increases in Lp(a) levels correlate with a heightened risk of cardiovascular events. Furthermore, Lp(a) plays a role in aortic stenosis by binding to leaflet valves, accumulating within them, and triggering calcium deposition and nodule formation. These calcium deposits gradually narrow the arteries, impeding blood flow. By raising inflammation and oxidative stress in the valve, Lp(a) accelerates tissue damage and calcium deposition. Traditional lipid-lowering therapies have limited efficacy in reducing Lp(a) levels. However, new treatments using RNA interference and antisense oligonucleotides to decrease Lp(a) production in the liver offer promising prospects for mitigating the risks and managing atherosclerosis and aortic stenosis associated with high Lp(a) levels. As Lp(a) screening becomes more common in healthcare, physicians will be better equipped to assess patients' risk levels and provide tailored treatments. This review aims to examine the role of Lp(a) in the development of aortic stenosis and atherosclerosis.

A Precision Medicine Guided Approach to the Utilization of Biomarkers in MASLD.

The new nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes a positive diagnosis based on cardiometabolic risk factors. This definition is not only less stigmatizing but also allows for subclassification and stratification, thereby addressing the heterogeneity of what was historically referred to as nonalcoholic fatty liver disease. The heterogeneity within this spectrum is influenced by several factors which include but are not limited to demographic/dietary factors, the amount of alcohol use and drinking patterns, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The net effect of this dynamic and intricate system-level interaction is reflected in the phenotypic presentation of MASLD. Therefore, the application of precision medicine in this scenario aims at complex phenotyping with consequent individual risk prediction, development of individualized preventive strategies, and improvements in the clinical trial designs. In this review, we aim to highlight the importance of precision medicine approaches in MASLD, including the use of novel biomarkers of disease, and its subsequent utilization in future study designs.

Encapsulation of Cinnamaldehyde and Vanillin as a Strategy to Increase Their Antimicrobial Activity.

Many studies have suggested that the encapsulation of natural antimicrobials increases their antimicrobial activity. In this sense, the objective was to study the inactivation of microorganisms with encapsulated cinnamaldehyde and vanillin (E-CIN and E-VN), in comparison with the unencapsulated antimicrobials (CIN and VN) in protein beverages. Additionally, the microbial response was quantified through mathematical modeling. Cinnamaldehyde and vanillin were encapsulated using whey protein concentrate (WPC) as the encapsulating agent. The effectiveness at inactivating Escherichia coli, Listeria innocua, and Saccharomyces cerevisiae was evaluated in a protein-apple juice beverage during storage (4 °C). Encapsulation increased the effectiveness of cinnamaldehyde, reaching reductions of 1.8, 3.3, and 5.3 log CFU/mL in E. coli, L. innocua, and S. cerevisiae, respectively, while vanillin encapsulation had little effect on antimicrobial activity, reducing by 0.5, 1.4, and 1.1 log cycles, respectively. The combined treatments (E-CIN + E-VN) had an additive effect in reducing E. coli and a synergistic effect against S. cerevisiae. The Gompertz model was more versatile and better described the biphasic curves, whereas the Weibull model complemented the information regarding the spectrum of resistances within the microbial population. In conclusion, the encapsulation of cinnamaldehyde with WPC enhanced its activity. However, further studies are necessary to improve the antimicrobial activity of vanillin.

The Cardiac Pulsed Wave Doppler Pattern of the Common Femoral Vein in Diagnosing the Likelihood of Severe Pulmonary Hypertension: Results from a Prospective Multicentric Study.

Background and Objectives: Pulmonary hypertension (PH) is a clinical condition with high mortality rates, particularly in patients over 65. Current guidelines recommend assessing the likelihood of pulmonary hypertension (LPH) using advanced echocardiography before proceeding to right heart catheterization. This study proposed using the common femoral vein (CFV), an accessible vein that reflects right atrial pressure, as an alternative method to assess the high likelihood of pulmonary hypertension (H-LPH). Materials and Methods: This prospective observational study included 175 emergency patients from three hospitals. Ultrasound assessed the pulsed wave Doppler (PW-Doppler) morphology of the CFV. This diagnostic yield for H-LPH was evaluated alongside traditional ultrasound parameters (right-to-left ventricular basal diameter ratio greater than 1 (RV > LV), septal flattening, right ventricular outflow acceleration time (RVOT) of less than 105 ms and/or mesosystolic notching, pulmonary artery diameter greater than the aortic root (AR) diameter or over 25 mm, early pulmonary regurgitation maximum velocity > 2.2 m/s; TAPSE/PASP less than 0.55, inferior vena cava (IVC) diameter over 21 mm with decreased inspiratory collapse, and right atrial (RA) area over 18 cm2). Results: The CFV's PW-Doppler cardiac pattern correlated strongly with H-LPH, showing a sensitivity (Sn) of 72% and a specificity (Sp) of 96%. RA dilation and TAPSE/PASP < 0.55 also played significant diagnostic roles. Conclusions: The CFV's PW-Doppler cardiac pattern is an effective indicator of H-LPH, allowing reliable exclusion of this condition when absent. This approach could simplify initial LPH evaluation in emergency settings or where echocardiographic resources are limited.

Adsorption Mechanism and Characteristic Temperatures of the Monolayer Adsorption of CO2 on Graphite: The Role of Graphene Dimensions.

Although simulation results for gaseous adsorption on a surface of infinite extent, modeled with periodic conditions at the boundaries of the simulation box, agree with experimental data at high temperatures, simulated isotherms at temperatures below the triple point temperature show unphysical substeps because of the compromise of interactions within the box and interactions between the box and its mirror image boxes. This has been alleviated with surfaces of finite dimensions (Loi, Q. K.; Colloids Surf., A 2021, 622, 126690 and Castaño Plaza, O.; Langmuir 2023, 39 (21), 7456-7468) to account for free boundaries at the adsorbate patch on the surface, and the critical parameter of this model substrate is the size of the finite surface. If it is too small, the adsorbate patch does not model the physical reality; however, if it is too large, the computation time is excessive, making the simulation impractical. In this study, we used carbon dioxide/graphite as the model system to explore the effects of finite dimensions on the description of experimental data of Terlain, A.; Larher, Y. Surf. Sci. 1983, 125 (1), 304-311, especially for temperatures below the bulk triple point temperature. With the appropriate choice of graphene size, we derived the 2D triple point and 2D critical point temperatures of the monolayer, and most importantly, for temperatures below the 2D critical point temperature, the adsorption mechanism for the formation of the monolayer is due to the interplay between the boundary growth process and the vacancy filling. The extent of this interplay is found to depend on the fractional coverage of the surface.

Physicochemical and Mechanical Properties of Non-Isocyanate Polyhydroxyurethanes (NIPHUs) from Epoxidized Soybean Oil: Candidates for Wound Dressing Applications.

Only 0.1% of polyurethanes available on the market are from renewable sources. With increasing concern about climate change, the substitution of monomers derived from petrochemical sources and the application of eco-friendly synthesis processes is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have been utilized, as their synthesis route allows for the carbonation of vegetable oils with carbon dioxide and the substitution of isocyanates known for their high toxicity, carcinogenicity, and petrochemical origin. In this study, polyhydroxyurethanes were obtained from carbonated soybean oil in combination with two diamines, one that is aliphatic (1,4-butadiamine (putrescine)) and another that is cycloaliphatic (1,3-cyclohexanobis(methylamine)). Four polyhydroxyurethanes were obtained, showing stability in hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9 and 1.1 MPa, an elongation at break between 81 and 222%, a water absorption rate up 102%, and contact angles between 63.70 and 101.39. New formulations of bio-based NIPHUs can be developed with the inclusion of a cycloaliphatic diamine (CHM) for the improvement of mechanical properties, which represents a more sustainable process for obtaining NIPHUs with the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.

An enhancer RNA recruits KMT2A to regulate transcription of Myb.

The Myb proto-oncogene encodes the transcription factor c-MYB, which is critical for hematopoiesis. Distant enhancers of Myb form a hub of interactions with the Myb promoter. We identified a long non-coding RNA (Myrlin) originating from the -81-kb murine Myb enhancer. Myrlin and Myb are coordinately regulated during erythroid differentiation. Myrlin TSS deletion using CRISPR-Cas9 reduced Myrlin and Myb expression and LDB1 complex occupancy at the Myb enhancers, compromising enhancer contacts and reducing RNA Pol II occupancy in the locus. In contrast, CRISPRi silencing of Myrlin left LDB1 and the Myb enhancer hub unperturbed, although Myrlin and Myb expressions were downregulated, decoupling transcription and chromatin looping. Myrlin interacts with the KMT2A/MLL1 complex. Myrlin CRISPRi compromised KMT2A occupancy in the Myb locus, decreasing CDK9 and RNA Pol II binding and resulting in Pol II pausing in the Myb first exon/intron. Thus, Myrlin directly participates in activating Myb transcription by recruiting KMT2A.

Global epidemiology of alcohol-associated liver disease in adolescents and young adults.

BACKGROUND AND AIMS: The objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time. METHODS: The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time. RESULTS: In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults. CONCLUSION: Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations.

Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary. METHODS: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data. RESULTS: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average. CONCLUSION: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.

Printability and Thermophysical Properties of Three-Dimensional-Printed Food Based on "Cochayuyo" Durvillaea antarctica Seaweed Flour.

This research assessed the feasibility of adding Cochayuyo seaweed flour (at 30, 50, and 70% levels) to rice flour-based paste to improve its 3D printing quality. The paste's rheological properties, printing quality, texture profile, thermal properties, and color of 3D-printed foods were explored. Results showed that pastes with Cochayuyo addition exhibited shear-thinning behavior, and viscosity increased with increased Cochayuyo concentration. Viscoelastic properties and a Texture Profile Analysis (TPA) revealed that Cochayuyo improved mechanical strength and made the paste easier to flow, improving printed food's extrudability, fidelity, and shape retention, which was better observed in RC50 and RC70 printed at 15 mm s-1. A differential scanning calorimetry (DSC) analysis showed a partial substitution of rice flour for Cochayuyo flour in the formulation. This increased the onset and melting peak temperatures and reduced the enthalpy of fusion. CIE color parameters a*, b*, and L* showed that Cochayuyo addition increased the color to yellow and red; however, lightness was considerably reduced. Therefore, Cochayuyo flour could have the potential to be used for the manufacture improvement of 3D-printed food with better rheological, mechanical, thermal, printing quality, and nutritional properties, making possible the exploitation of the native Cochayuyo seaweed, which is highly available in Chile.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.